Social isolation and loneliness increase heart disease risk in senior women

by University of California - San Diego

As social networks shrink, older adults are more at risk for social isolation and loneliness. Credit: Herbert Wertheim School of Public Health and Human Longevity Science at University of California San Diego

During the current pandemic, social distancing has been one tool used to reduce the spread of COVID-19. But data from a new study point to as much as a 27% increase in heart disease risk in postmenopausal women who experience both high levels of social isolation and loneliness.

20 feb 2022--The findings of the prospective study, published in the February 2, 2022 online issue of JAMA Network Open, reveal that social isolation and loneliness independently increased cardiovascular disease risk by 8% and 5% respectively. If women experienced high levels of both, their risk rose 13% to 27% compared to women who reported low levels of social isolation and low levels of loneliness.

"We are social beings. In this time of COVID-19, many people are experiencing social isolation and loneliness, which may spiral into chronic states," said first author Natalie Golaszewski, Ph.D., a postdoctoral scholar at the Herbert Wertheim School of Public Health and Human Longevity Science at University of California San Diego. "It is important to further understand the acute and long-term effects these experiences have on cardiovascular health and overall well-being."

Importantly, social isolation and loneliness are mildly correlated and can occur at the same time, but they are not mutually exclusive. A socially isolated person is not always lonely and conversely a person experiencing loneliness is not necessarily socially isolated.

"Social isolation is about physically being away from people, like not touching or seeing or talking to other people. Loneliness is a feeling, one that can be experienced even by people who are regularly in contact with others," said senior author John Bellettiere, Ph.D., M.P.H., assistant professor of epidemiology at the Herbert Wertheim School of Public Health.

Social isolation and loneliness are a growing public health concern as they are associated with health conditions that increase the risk of cardiovascular disease including obesity, smoking, physical inactivity, poor diet, high blood pressure and high cholesterol.

When researchers included all of these health behaviors and conditions in their study and adjusted for diabetes and depression, high social isolation and loneliness remained strongly linked with increased risk for heart disease, supporting the importance of studying these social conditions.

According to the Centers for Disease Control and Prevention, heart disease is the leading cause of death for women in the United States, responsible for 1 in every 5 deaths.

As social networks shrink, older adults are more at risk for social isolation and loneliness, wrote the authors. One-fourth of adults 65 and older report social isolation and one-third of adults 45 or older report being lonely.

"We do not yet know whether the increased risk of cardiovascular disease is due to acute exposure to social isolation and loneliness or whether prolonged exposure accumulated over a lifetime is the culprit. Further studies are needed to better understand that," said Bellettiere.

Previous research indicates women experience more social isolation than men.

For this study, 57,825 postmenopausal women living in the United States who had previously participated in the Women's Health Initiative study responded to questionnaires assessing social isolation from 2011 to 2012. They were sent a second questionnaire assessing loneliness and social support in 2014 to 2015.

Participants were followed from the time of the questionnaire completion through 2019 or when they were diagnosed with cardiovascular disease. A total of 1,599 women experienced cardiovascular disease.

"Measures of social isolation and loneliness—even with brief questions as was done in our study—should be incorporated into standard care," said Golaszewski. "We monitor our patients' blood pressure, weight and temperature, and it might also be beneficial to capture the social needs that individuals may be lacking to better understand cardiovascular risk and develop solutions."

Individuals who feel lonely or socially isolated can find information about steps to help reduce these feelings from the National Institute on Aging.

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More information: Evaluation of Social Isolation, Loneliness, and Cardiovascular Disease Among Older Women in the US, JAMA Network Open (2022). DOI: 10.1001/jamanetworkopen.2021.46461

Provided by University of California - San Diego 

 

Midlife chronic conditions linked to increased dementia risk later in life

by British Medical Journal

Credit: CC0 Public Domain

Having two or more chronic conditions (known as multimorbidity) in middle age is associated with an increased risk of dementia later in life, finds a large study of British adults, published by The BMJ today.

20 feb 2022--Common chronic conditions include high blood pressure, diabetes, coronary heart disease, depression, and chronic lung disease (COPD). The results show that the risk is greater when these sorts of conditions develop at a younger age (mid-50s) rather than later in life.

Evidence shows that multimorbidity is common, particularly at older ages and in people living with dementia. But studies examining whether multimorbidity at earlier ages affects the risk of subsequent dementia are lacking.

To fill this knowledge gap, researchers set out to examine the long term association between multimorbidity at ages 55, 60, 65, and 70 and subsequent dementia.

Their findings are based on data collected from over 10,000 British men and women taking part in the Whitehall II Study, which is looking at the association of social, behavioral, and biological factors on long term health. When participants joined the study in 1985-88, they were aged 35 to 55 and were free of dementia.

For this study, multimorbidity was defined as the presence of at least two chronic conditions out of a predefined list of 13 chronic diseases, excluding dementia. Subsequent cases of dementia were identified using hospital and death records up to 31 March 2019.

Of the 10,095 participants, 6.6% had multimorbidity at age 55 and 32% at age 70. Over a median follow-up period of 32 years, 639 cases of dementia were identified.

After taking account of a range of factors including age, sex, ethnicity, education, diet and lifestyle behaviors, multimorbidity at age 55 was associated with a 2.4-fold higher risk of dementia (1.56 per 1,000 person years) compared with people without any of the 13 chronic conditions.

This association weakened progressively with older age at onset of multimorbidity.

For example at age 65, onset of multimorbidity before age 55 was associated with a 2.5-fold higher risk of dementia (3.86 per 1,000 person years) compared with a 1.5-fold higher risk (1.85 per 1,000 person years) in those with onset of multimorbidity between age 60 and 65.

In other words, for every 5 year younger age at onset of multimorbidity up to age 70, the risk of dementia was 18% higher.

When the researchers examined more severe multimorbidity (defined as three or more chronic conditions), the importance of younger age of onset of multimorbidity for the risk of dementia was further accentuated.

For example, compared with people with no or one chronic condition, those with three or more chronic conditions at age 55 had a nearly fivefold higher risk of dementia, whereas the risk was 1.7-fold higher when onset of multimorbidity was at age 70.

This is an observational study, so can't establish cause, and the researchers point to some limitations, such as possible misclassification of some dementia cases, and the fact that study participants are likely to be healthier than the general population.

However, this was a large study with over 30 years of follow-up, and results were similar after further analyses using death as the outcome measure, which the researchers say increases confidence in their findings on dementia.

"Given the lack of effective treatment for dementia and its personal and societal implications, finding targets for prevention of dementia is imperative," they write. "These findings highlight the role of prevention and management of chronic diseases over the course of adulthood to mitigate adverse outcomes in old age."

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More information: Association between age at onset of multimorbidity and incidence of dementia: 30 year follow-up in Whitehall II prospective cohort study, BMJ (2022). DOI: 10.1136/bmj-2021-068005

Provided by British Medical Journal 

 

Anxiety and alcohol misuse among pandemic-related mental health challenges Americans face

by Barri Bronston, Tulane University

Credit: Tulane School of Social Work Study

More than two years into the COVID-19 pandemic, behavioral health concerns continue to disrupt the lives of Americans, and addressing those concerns should be a major priority, according to a study by the Tulane University School of Social Work.

20 feb 2022--Published recently in the journal Scientific Reports, research from Patrick Bordnick, dean of the School of Social Work, and Tonya Hansel, a disaster mental health expert who oversees the school's doctorate program, says that despite vaccinations and lifted restrictions, mental health issues continue to be a crucial concern as the pandemic enters a recovery phase.

"We found increased anxiety, depression and alcohol misuse and that the pandemic exacerbated prior problems," Hansel said.

"While many are looking forward to their new normal or returning to pre-pandemic lifestyle, continued threat, vaccine uncertainties and strain variation serve as cautionary reminders that the global pandemic is ongoing," she said. "Regardless of how long it takes for full recovery, more than a year of heightened fears, loneliness, economic consequences, and grief suggest that behavioral health will have longer term consequences."

In addition to Hansel and Bordnick, others on the team include Leia Saltzman, assistant professor of social work; Pamela Melton, professor of practice; and Tanisha Clark, a licensed clinical social worker.

Researchers surveyed Americans from more than 30 states and representing a wide range of ages, ethnicities, educational backgrounds and income levels. Although more than a quarter of respondents reported having mental health problems before the pandemic, mental health challenges during the pandemic rose to 33 percent.

Anxiety increased by 47 percent, while depression was up by 9 percent. Respondents also reported an 8 percent increase in alcohol misuse.

More than a third of respondents reported such COVID-19 experiences as social isolation, working from home, loss of income and children and teens being out of school. Participants noting social isolation and personal health effects had higher anxiety and depression and lower quality of life. Participants with suspected or diagnosed COVID-19 reported more alcohol misuse and lower quality of life.

The survey data is from early in the pandemic, and Hansel said Americans continue to experience mental health challenges related to it.

"We are seeing issues now and will see more behavioral health issues for years to come," Bordnick said. "Increased rates of relapse and new cases are growing each day."

Hansel agreed. "In disaster mental health, when the threat has dissipated and individuals move out of survival mode, behavioral health problems become more apparent, and consequently, services, such as psychoeducation, therapy and brief treatments, are needed."

"Prior to the pandemic, we had a shortage of mental health professionals. Now that the need has increased, the shortage is more dire," Bordnick said. "Our hope is that this data raises awareness around the urgency to fund accessible behavioral health services to address preexisting needs as well the emerging stress and anxiety related to the pandemic."

The study says an "urgent need" exists for enhanced behavior health services, including brief interventions to normalize symptoms, raise awareness of risk factors and teach coping skills.

The study also suggests that gains made toward telehealth over the past year can continue and increase access to mental health services.

"At this point in the disaster, more intensive treatments should also be made available, especially for those who exhibit specific risk factors, such as young and middle-aged adults, those with limited income and prior behavioral health concerns, and those living in communities with poorer health," Bordnick said.

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More information: Tonya Cross Hansel et al, COVID-19 behavioral health and quality of life, Scientific Reports (2022). DOI: 10.1038/s41598-022-05042-z

Provided by Tulane University 

 

Small study finds Alzheimer's-like changes in some COVID patients' brains

by Columbia University Irving Medical Center

Credit: Unsplash/CC0 Public Domain

A study from researchers at Columbia University Vagelos College of Physicians and Surgeons reports that the brains of a small sample of patients who died of COVID display some of the same molecular changes found in the brains of people with Alzheimer's disease.

20 feb 2022--The findings could help explain the memory problems reported by sufferers of "long COVID," though the researchers caution that the study is small—with data from only 10 patients—and needs to be replicated by others.

The study was published Feb. 3 in Alzheimer's & Dementia: The Journal of the Alzheimer's Association.

Early reports of "brain fog" and persistent cardiac symptoms in COVID survivors prompted the Columbia researchers to investigate how certain molecules called ryanodine receptors were affected in this new disease.

Defective ryanodine receptors have been implicated in diverse pathogenic processes, ranging from heart and lung disease to the brain's response to stress and Alzheimer's disease, as reported in research led by Andrew Marks, MD, chair of the Department of Physiology & Cellular Biophysics at the Vagelos College of Physicians and Surgeons, who led the new study.

"When the COVID pandemic hit, like everybody else I was interested in being helpful and doing what we could do," says Marks. "What we found is really I think quite unexpected: Not only did we find defective ryanodine receptors in the hearts and lungs of deceased COVID patients, we also found them in their brains."

Molecular changes

Inside neurons, defective ryanodine receptors have previously been linked to an increase in phosphorylated tau, a well-known hallmark of Alzheimer's.

In the new study, the Columbia researchers found high levels of phosphorylated tau in the brains of the COVID patients in addition to defective ryanodine receptors.

Phosphorylated tau was found in areas where tau is typically located in Alzheimer's patients, as well as in areas where tau is not typically located in Alzheimer's patients. That suggests that phosphorylated tau in the COVID patients could be a sign of early-stage Alzheimer's and also contribute to other neurological symptoms observed in COVID-19 patients.

Increased levels of phosphorylated tau in the brain are believed to be linked to memory problems in Alzheimer's and could be causing similar issues in people with long COVID, Marks says.

Based on the findings, together with additional changes found in the brain, the investigators theorize that the immune response characteristic of severe COVID causes inflammation in the brain, which in turn leads to dysfunctional ryanodine receptors and then increases in phosphorylated tau. No changes in the pathways that lead to the formation of amyloid beta—another hallmark of Alzheimer's—were found.

Future directions

"One interpretation of these findings is that long COVID could be an atypical form of Alzheimer's and/or that patients who had severe COVID could be predisposed to developing Alzheimer's later in life," says Marks, "but much more research needs to be done before we can make more definitive conclusions."

If the memory and neurological problems of long COVID can be traced to defective ryanodine receptors, a drug under development by Marks may help. The drug is now in early clinical trials to treat a muscle disease caused by an inherited defect in the ryanodine receptor. The drug was able to fix the ryanodine defect when applied to the COVID patients' brain tissue.

"My greatest hope is that other laboratories will look into our findings, and if they are validated, generate interest in a clinical trial for long COVID," says Marks.

More information: Steve Reiken et al, Alzheimer's‐like signaling in brains of COVID‐19 patients, Alzheimer's & Dementia (2022). DOI: 10.1002/alz.12558

Provided by Columbia University Irving Medical Center 

 

No time to exercise? What about three seconds a day?

by Edith Cowan University

Credit: Pexels

Lifting weights for as little as three seconds a day can have a positive impact on muscle strength, a new study from Edith Cowan University (ECU) has discovered.

20 feb 2022--A collaboration with researchers from Niigata University of Health and Welfare (NUHW) in Japan had 39 healthy university students perform one muscle contraction at maximum effort for three seconds per day, for five days a week over four weeks.

The participants performed either an isometric, concentric or eccentric bicep curl (see definitions below) at maximum effort, while researchers measured the muscles' maximum voluntary contraction strength before and after the four-week period.

Another 13 students performed no exercise over the same period and were also measured before and after the four weeks.

Muscle strength increased more than 10 percent for the group who performed the eccentric bicep curl after the four weeks, but less increase in muscle strength was found for the other two exercise groups.

The no exercise group saw no increase.

Lead researcher Professor Ken Nosaka from ECU's School of Medical and Health Sciences said the results showed people didn't need to spend vast amounts of time exercising to improve their muscle strength.

"The study results suggest that a very small amount of exercise stimulus—even 60 seconds in four weeks—can increase muscle strength," he said.

"Many people think you have to spend a lot of time exercising, but it's not the case. Short, good quality exercise can still be good for your body and every muscle contraction counts."

Isometric vs concentric vs eccentric

These three classifications relate to what the muscle is doing when being activated.

An isometric contraction is when the muscle is stationary under load, concentric is when the muscle is shortening and eccentric when the muscle is lengthening.

For a bicep curl, a dumbbell held with an arm by one's side, before lifting the weight upwards towards the chest and then lowering it back down via the elbow.

Lifting the weight sees the bicep in concentric contraction, lowering the weight sees it in eccentric contraction, while holding the weight parallel to the ground is isometric.

So which is best?

The study shows all three lifting methods had some benefit to muscle strength, however eccentric contraction easily produced the best results.

Researchers measured each group's concentric, isometric and eccentric strength.

The concentric lifting group improved slightly (6.3 percent) in isometric strength but saw no improvement elsewhere, while the isometric group only saw an increase in eccentric strength (7.2 percent).

However, the eccentric group saw significant improvements in strength across all three measurements: concentric increased 12.8 percent, isometric 10.2 percent and eccentric 12.2 percent.

The eccentric group's overall muscle strength improved 11.5 percent after 60 seconds of effort in total.

"Although the mechanisms underpinning eccentric contraction's potent effects are not clear yet, the fact only a three-second maximal eccentric contraction a day improves muscle strength in a relatively short period is important for health and fitness," Professor Nosaka said.

Time-poor no more

Professor Nosaka said the findings were exciting for promoting physical fitness and health, such as prevention of sarcopenia—a decrease in muscle mass and strength with aging.

"We haven't investigated other muscles yet, but if we find the three-second rule also applies to other muscles then you might be able to do a whole-body exercise in less than 30 seconds," he said.

"Also, performing only one maximal contraction per day means you don't get sore afterwards."

Professor Nosaka and NUHW's Dr. Masatoshi Nakamura designed the study and the data were collected by Dr. Nakamura and his Ph.D. and Masters students.

"Effect of daily 3-s maximum voluntary isometric, concentric or eccentric contraction on elbow flexor strength" was published in the Scandinavian Journal of Medicine and Science in Sports.

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More information: Shigeru Sato et al, Effect of daily 3‐s maximum voluntary isometric, concentric or eccentric contraction on elbow flexor strength, Scandinavian Journal of Medicine & Science in Sports (2022). DOI: 10.1111/sms.14138

Provided by Edith Cowan University 

 

Analysis shows that COVID-19 infections increase risk of heart conditions up to a year later

by Kristina Sauerwein, Washington University in St. Louis

Credit: Pixabay/CC0 Public Domain

An in-depth analysis of federal health data indicates that people who have had COVID-19 are at increased risk of developing cardiovascular complications within the first month to a year after infection. Such complications include disruptive heart rhythms, inflammation of the heart, blood clots, stroke, coronary artery disease, heart attack, heart failure or even death.

20 feb 2022--Such problems occur even among previously healthy individuals and those who have had mild COVID-19 infections, according to the study, from researchers at Washington University School of Medicine in St. Louis and the Veterans Affairs St. Louis Health Care System.

The research is published Feb. 7 in Nature Medicine.

"We wanted to build upon our past research on COVID's long-term effects by taking a closer look at what's happening in people's hearts," said senior author Ziyad Al-Aly, MD, an assistant professor of medicine at Washington University. "What we're seeing isn't good. COVID-19 can lead to serious cardiovascular complications and death. The heart does not regenerate or easily mend after heart damage. These are diseases that will affect people for a lifetime."

More than 380 million people globally have been infected with the virus since the pandemic started.

"Consequently, COVID-19 infections have, thus far, contributed to 15 million new cases of heart disease worldwide," said Al-Aly, who treats patients within the VA St. Louis Health Care System. "This is quite significant. For anyone who has had an infection, it is essential that heart health be an integral part of post-acute COVID care."

Cardiovascular disease—an umbrella term that refers to various heart conditions, thrombosis and stroke—is the leading cause of death in the United States and the world. The Centers for Disease Control and Prevention (CDC) estimates that one out of every four Americans dies of heart disease each year.

Additionally, heart disease comes with a hefty price tag, according to the CDC, costing the U.S. about $363 billion each year in health-care services, medications and productivity lost to death.

"For people who were clearly at risk for a heart condition before becoming infected with SARS-CoV-2, the findings suggest that COVID-19 may amplify the risk," said Al-Aly, who is also director of the Clinical Epidemiology Center and chief of the Research and Education Service at the Veterans Affairs St. Louis Health Care System.

"But most remarkably, people who have never had any heart problems and were considered low risk are also developing heart problems after COVID-19," he added. "Our data showed an increased risk of heart damage for young people and old people; males and females; Blacks, whites and all races; people with obesity and people without; people with diabetes and those without; people with prior heart disease and no prior heart disease; people with mild COVID infections and those with more severe COVID who needed to be hospitalized for it."

The researchers analyzed de-identified medical records in a database maintained by the U.S. Department of Veterans Affairs, the nation's largest integrated health-care delivery system. The researchers created a controlled dataset that included health information of 153,760 people who had tested positive for COVID-19 sometime from March 1, 2020, through Jan. 15, 2021, and who had survived the first 30 days of the disease. Very few of the people in the study were vaccinated prior to developing COVID-19, as vaccines were not yet widely available at the time of enrollment.

Statistical modeling was used to compare cardiovascular outcomes in the COVID-19 dataset with two other groups of people not infected with the virus: A control group of more than 5.6 million patients who did not have COVID-19 during the same time frame; and a control group of more than 5.8 million people who were patients from March 2018 through January 2019, well before the virus spread and the pandemic settled in.

The study does not include data involving the virus's Delta and Omicron variants, which began spreading rapidly in the latter half of 2021.

The COVID-19 patients in the study were mostly older, white men; however, the researchers also analyzed data that included women and adults of all ages and races.

The researchers analyzed heart health over a year-long period. Heart disease, including heart failure and death, occurred in 4% more people than those who had not been infected with COVID-19.

"Some people may think 4% is a small number, but it's not, given the magnitude of the pandemic," Al-Aly said. "That translates to roughly 3 million people in the U.S. who have suffered cardiovascular complications due to COVID-19."

Compared with those in the control groups without any infections, people who contracted COVID-19 were 72% more likely to suffer from coronary artery disease, 63% more likely to have a heart attack and 52% more likely to experience a stroke.

Overall, those infected with the virus were 55% more likely than those without COVID-19 to suffer a major adverse cardiovascular event, which includes heart attack, stroke and death.

"Our findings highlight the serious long-term cardiovascular consequences of having a COVID-19 infection and emphasize the importance of getting vaccinated against COVID-19 as a way to prevent heart damage; this also underscores the importance of increasing accessibility to the vaccines in countries with limited resources," Al-Aly said.

"Governments and health systems around the world should be prepared to deal with the likely significant contribution of the COVID-19 pandemic to a rise in the burden of cardiovascular diseases," he said. "Because of the chronic nature of these conditions, they will likely have long-lasting consequences for patients and health systems, and also have broad implications on economic productivity and life expectancy. Addressing the challenges posed by long-COVID will require a much-needed—but so far lacking—urgent and coordinated long-term global response strategy."

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More information: Yan Xie et al, Long-term cardiovascular outcomes of COVID-19, Nature Medicine (2022). DOI: 10.1038/s41591-022-01689-3

Provided by Washington University in St. Louis 

 

Natural mineral may help reverse memory loss

by University of Queensland

Credit: Pixabay/CC0 Public Domain

Selenium—a mineral found in many foods—could reverse the cognitive impact of stroke and boost learning and memory in aging brains, according to University of Queensland research.

20 feb 2022--Queensland Brain Institute (QBI) lead researcher Dr. Tara Walker said studies on the impact of exercise on the aging brain found levels of a protein key to transporting selenium in the blood were elevated by physical activity.

"We've known for the last 20 years that exercise can create new neurons in the brain, but we didn't really understand how," Dr. Walker said.

The research team investigated whether dietary selenium supplements could replicate the effects of exercise.

"Our models showed that selenium supplementation could increase neuron generation and improve cognition in elderly mice," Dr. Walker said.

"The levels of new neuron generation decrease rapidly in aged mice, as they do in humans.

"When selenium supplements were given to the mice, the production of neurons increased, reversing the cognitive deficits observed in aging."

Selenium is an essential trace mineral absorbed from soil and water and is found in foods such as grains, meat and nuts, with the highest levels found in Brazil nuts.

The scientists also tested whether selenium would have an impact on the cognitive decline sometimes experienced following stroke, which can affect people's memory and ability to learn.

"Young mice are really good at the learning and memory tasks, but after a stroke, they could no longer perform these tasks," Dr. Walker said.

"We found that learning and memory deficits of stroke affected mice returned to normal when they were given selenium supplements."

Dr. Walker said the results opened a new therapeutic avenue to boost cognitive function in people who were unable to exercise due to poor health or old age.

"However, selenium supplements shouldn't be seen as a complete substitute for exercise, and too much can be bad for you," she said.

"A person who is getting a balanced diet of fruits, nuts, veggies and meat usually has good selenium levels.

"But in older people, particularly those with neurological conditions, selenium supplements could be beneficial."

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More information: Odette Leiter et al, Selenium mediates exercise-induced adult neurogenesis and reverses learning deficits induced by hippocampal injury and aging, Cell Metabolism (2022). DOI: 10.1016/j.cmet.2022.01.005

Provided by University of Queensland 

 

Loneliness associated with increased risk of dementia in older adults

by NYU Langone Health

Chart showing incident of dementia for adults under age 80 without APOE ε4 allele, a genetic risk factor for Alzheimer's disease. Credit: NYU Langone Health

As social isolation in the United States has been increasing among older adults, a new study shows a notable link between loneliness and dementia risk, and one that is most striking for Americans who represent a large part of the population.

20 feb 2022--In the study publishing February 7 in Neurology, the medical journal of the American Academy of Neurology, researchers found a three-fold increase in risk of subsequent dementia among lonely Americans younger than 80 years old who would otherwise be expected to have a relatively low risk based on age and genetic risk factors. The study also found that loneliness was associated with poorer executive function (i.e., a group of cognitive processes including decision-making, planning, cognitive flexibility, and control of attention) and changes in the brain that indicate vulnerability to Alzheimer's disease and related dementias (ADRD).

"This study emphasizes the importance of loneliness and issues of social connection in addressing our risk of developing dementia as we age," says lead investigator Joel Salinas, MD, MBA, MSc, the Lulu P. and David J. Levidow Assistant Professor of Neurology at NYU Grossman School of Medicine and member of the Department of Neurology's Center for Cognitive Neurology. "Acknowledging signs of loneliness in yourself and others, building and maintaining supportive relationships, providing much-needed support for the people in our lives who are feeling lonely—these are important for everyone. But they're especially important as we age to increase the chances that we'll delay or perhaps even prevent cognitive decline."

Dementia affects more than 6.2 million adults in the United States, according to a 2021 special report by the Alzheimer's Association. Since the beginning of the coronavirus pandemic, feelings of loneliness have affected an estimated 46 million Americans, and more frequent feelings of loneliness were found in adults aged 60 and older.

"This study is a reminder that, if we want to prioritize brain health, we can't ignore the role of psychosocial factors like loneliness and the social environments we live in day-to-day," says Dr. Salinas. "Sometimes, the best way to take care of ourselves and the people we love is simply to regularly reach out and check in—to acknowledge and be acknowledged."

Dr. Salinas adds, "We can share with each other when we're feeling lonely, appreciate with each other how loneliness is common, and accept that giving and asking for support can be hard. Fortunately, loneliness can be cured. And although we might need to be vulnerable and creative in figuring out new ways to connect, chances are that even the smallest gesture will have been worth it."

How the Study Was Conducted

Using retrospective data of the population-based Framingham Study (FS), researchers reviewed 2,308 participants who were dementia-free at baseline, with an average age of 73. Neuropsychological measures and MRI brain scans were obtained at examination and participants were asked how often they felt lonely along with other depressive symptoms, such as restless sleep or poor appetite. Participants were also assessed for the presence of a genetic risk factor for Alzheimer's disease called the APOE ε4 allele. Overall, 144 of the 2,308 participants reported feeling lonely three or more days in the past week.

The study population was assessed over a decade for dementia using rigorous clinical methods, and 329 of the 2,308 participants were subsequently diagnosed with the disease. Among the 144 lonely participants, 31 developed dementia. While there was no significant association between loneliness and dementia in participants aged 80 years or older, younger participants aged 60 to 79 who were lonely were more than twice as likely to develop dementia. Loneliness was associated with three-fold increased risk among younger participants who did not carry the APOE ε4 allele.

Researchers concluded that the tripling in risk was possibly related to associations between loneliness and early cognitive and neuroanatomical markers of ADRD vulnerability, raising potential population health implications for observed trends in loneliness. Additional findings showed that loneliness was related with poorer executive function, lower total cerebral volume, and greater white-matter injury, which are indicators of vulnerability for cognitive decline.

In addition to Dr. Salinas, researchers from the Boston University School of Public Health, Boston University School of Medicine, University of California Davis, and the Biggs Institute for Alzheimer's and Neurodegenerative Diseases at the University of Texas Health Sciences Center San Antonio were also involved in the study.

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More information: Association of Loneliness With 10-Year Dementia Risk and Early Markers of Vulnerability for Neurocognitive Decline, Neurology (2022). DOI: 10.1212/WNL.0000000000200039

Provided by NYU Langone Health 

 

Viagra-like drugs may play role in treating dementia

by St. George's University of London

Example of anatomical and cerebral blood flow (CBF) mapping, with tissue segmentation. A, Fluid-attenuated inversion recovery (FLAIR) image at full resolution. B, FLAIR image co-registered to the CBF map, with voxels re-sized to be equivalent to the pseudo-continuous arterial spin labeling (pCASL) map. C, CBF map, derived from pCASL. Calibration bar shows 0.0–80.0 mL/min/100 g. D, Tissue segmentation map for CBF computation. Each voxel has been defined as either: cerebrospinal fluid (CSF), gray matter (GM), normal-appearing white matter (WM), or white matter hyperintensity (WMH). E, F, Probability density functions of CBF values in voxels assigned as gray matter (E) or normal-appearing white matter (F). For this participant, median CBF was 51.3 mL/min/100 g in gray matter and 21.8 mL/min/100 g in normal-appearing white matter. Credit: DOI: 10.1002/alz.12559

A new study, published today in Alzheimer's & Dementia, tested whether tadalafil, a drug closely related to Viagra, may be effective in treating people with vascular dementia.

20 feb 2022--The phase II trial, led by researchers at St George's, University of London and St George's Hospital was joint-funded by the US-based Alzheimer's Drug Discovery Foundation and the UK Alzheimer's Society. The trial tested whether tadalafil increases brain blood flow in older men and women with narrowing of the brain arteries, a condition that can cause strokes and vascular dementia.

Although the trial results found no significant increase in blood flow, the researchers found clues pointing towards a potential use for tadalafil in treating certain groups of patients, warranting further investigation.

Dementia is an escalating global healthcare challenge, estimated to affect 55 million people worldwide, increasing to 139 million by 2050. There are few treatment options for patients, and the new trial explored whether repurposing an existing drug, tadalafil, may have potential for treating vascular dementia—a common type of dementia in which there is reduced blood flow to the brain.

A recent computational analysis identified sildenafil (Viagra) and vardenafil, drugs commonly used to increase blood flow in erectile dysfunction and in pulmonary hypertension (a form of lung disease), as possible candidates for preventing or delaying dementia.

Tadalafil belongs to the same group of drugs, and the researchers hypothesize that the mechanisms that increase blood flow in other parts of the body, may also apply in the brain—providing brain cells with a healthier blood supply and reducing dementia symptoms.

Tadalafil was selected as the drug candidate for the trial because of its longer half-life (remaining in the bloodstream for longer) and evidence that it is better able to enter the brain, than its related drugs.

The trial compared a single dose of tadalafil with placebo, recording brain blood flow using an MRI-based method called arterial spin labeling, which traces blood flow without the need for radioactive tracers.

The investigators did not detect a significant difference in blood flow between those given tadalafil and those given a placebo. However, the results did show a trend for increased blood flow in older participants (those aged over 70) in the white matter of the brain, which is the area most important for vascular dementia.

No serious adverse events were recorded during the trial.

The research team believe further investigation of tadalafil should be considered to explore its effectiveness in older age groups over a longer time period.

Dr. Jeremy Isaacs, principal clinical investigator on the trial and consultant neurologist at St George's Hospital, said: "Narrowing of the brain arteries is a common contributor to cognitive decline in older people and currently has no treatment. This was a landmark study in which we attempted to reverse the reduction in brain blood flow characteristic of this condition. Although we did not find a significant effect following a single dose of tadalafil, we can't rule out the possibility of benefits from longer term use, for which further research is needed."

Dr. Atticus Hainsworth, lead investigator on the trial and Reader in Cerebrovascular disease at St George's, University of London, said: "Viagra-like drugs merit further investigation for possible use in dementia. Repurposed drugs have the increased benefits of a shorter development time, a known safety profile and low cost, once their original patent has expired. We hope that further investigations will prove fruitful and provide new options for clinicians treating dementia."

Katherine Gray, Research Communications Manager at Alzheimer's Society, said: "Sadly, for the 900,000 people living with dementia in the UK, there aren't any current drugs to stop dementia progressing. Using existing medications, such as Viagra-like drugs, could shave decades off our search for treatments because they are already shown to be safe for people to use.

"Although it's disappointing that tadalafil did not have a significant effect overall, it's promising that people over the age of 70 did have an increase in blood flow to certain areas of the brain, and we now hope to now see further tests for different doses over a longer period of time."

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More information: Mathilde M.H. Pauls et al, The PASTIS trial: Testing tadalafil for possible use in vascular cognitive impairment, Alzheimer's & Dementia (2022). DOI: 10.1002/alz.12559

Provided by St. George's University of London 

 

Researchers introduce into human cells a genetic mutation that protects against Alzheimer's disease

by Laval University

Credit: Pixabay/Pete Linforth.

Researchers from the Université Laval Faculty of Medicine and CHU de Québec–Université Laval Research Center have successfully edited the genome of human cells grown in vitro to introduce a mutation providing protection against Alzheimer's disease. The details of this breakthrough were recently published in The CRISPR Journal.

20 feb 2022--"Some genetic mutations increase the risk of developing Alzheimer's disease, but there is a mutation that reduces this risk," says lead author Professor Jacques-P. Tremblay. "This is a rare mutation identified in 2012 in the Icelandic population. The mutation has no known disadvantage for those who carry it and reduces the risk of developing Alzheimer's disease. Using an improved version of the CRISPR gene editing tool, we have been able to edit the genome of human cells to insert this mutation."

The brains of those with Alzheimer's present amyloid plaques, which have a level of toxicity believed to cause neuron death. These plaques are formed when the amyloid precursor protein is cleaved by an enzyme called beta-secretase. "The Icelandic mutation makes it harder for this enzyme to cleave the amyloid precursor protein. As a result, the formation of amyloid plaques is reduced," explains Professor Tremblay.

In theory, introducing the Icelandic mutation into the genome of people at risk of developing Alzheimer's could prevent or slow the progression of the disease. "Unfortunately, we can't go back and repair the damage that caused neurons to die," says the researcher. "The treatment would therefore be particularly suitable for people from families affected by the hereditary form of the disease, which manifests itself in memory problems from the age of 35 to 40. If successful, it could also potentially be used to treat people with the most common form of Alzheimer's, which occurs after age 65, at the earliest signs of the disease."

"The challenge now is to find a way to edit the genome of millions of brain cells," says Professor Tremblay. "We are looking at different possibilities, including the use of non-infectious viruses, to deliver the editing complex inside neurons. Now that the proof of concept has been established in human cells in vitro, we will test this approach in mice that express Alzheimer's disease. If the findings are conclusive, we hope to be able to conduct a small-scale study in people with mutations that cause the onset of Alzheimer's at age 35 to 40."

In addition to Jacques-P. Tremblay, the authors of the study published in The CRISPR Journal are Guillaume Tremblay, Joël Rousseau, and Cédric Mbakam.

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More information: Guillaume Tremblay et al, Insertion of the Icelandic Mutation (A673T) by Prime Editing: A Potential Preventive Treatment for Familial and Sporadic Alzheimer's Disease, The CRISPR Journal (2022). DOI: 10.1089/crispr.2021.0085

Provided by Laval University 

 

Older people in good shape have fitter brains

by Anders Revdal, Norwegian University of Science and Technology

How should older people train to get in better shape? What’s most important, according to the researchers, is that you find an activity that you enjoy and can continue doing over time. Credit: Erlend Lånke Solbu / NRK

Seventy- to eighty-year-olds who train for better fitness are better at solving cognitive tasks and are less likely to suffer cognitive impairment.

20 feb 2022--"Our findings suggest that being fit can protect against mild cognitive impairment in older people," says Ekaterina Zotcheva.

Just before Christmas, Zotcheva defended her doctoral dissertation on exercise and brain health at NTNU. The day before the defense, the last study for her doctoral degree was published in the Sports Medicine journal.

The article is just one of three recent research articles from NTNU that show how important it is for the brain to stay in good physical shape as you get older. Common to all three articles is that they are based on data from the world's largest training study for older adults, the Generation 100 study from the Cardiac Exercise Research Group.

Dementia risk

"The Generation 100 study has been going on for almost ten years now. After the study participants had been exercising for five years, we tested the cognitive function of almost 1,000 of them."

"The men and women who had maintained or increased their physical fitness during the study had better brain health than those whose fitness had declined over the five years," says Zotcheva.

The cognitive test that the participants took is the same one that is often used to check whether people are at risk of developing dementia.

The test assesses short-term memory, execution function and the ability to orient oneself in time and space. Scoring below a certain number indicates a risk of mild cognitive impairment.

"We know that mild cognitive impairment can lead to dementia for some individuals. The greater the increase in a participant's fitness level during the five years of the study, the lower their probability was of developing mild cognitive impairment," says Zotcheva.

Better at problem solving

Good conditioning appears to be an important prerequisite for good brain function in the elderly in the other two research articles as well. In both of these studies, the researchers tested the brain health of more than 100 of the participants in the Generation 100 study at start-up and after one, three and five years of training.

"Participants who were in good shape, both when the study started and later in the study, had a faster reaction time. The ones who improved their fitness level gained a somewhat better working memory," says NTNU professor Asta Håberg.

The ability to solve cognitive problems was tested using the web-based Memoro platform, which Håberg developed in collaboration with neuropsychologist Tor Ivar Hansen.

Less brain atrophy

Håberg has been involved in the work with all three recent research articles. In the third study, the researchers performed MRI scans of the participants' brains to see how the brain volume and thickness of the cerebral cortex changed throughout the study. Here, too, the most energetic participants came out best.

"Participants who were in good shape when the study started had a thicker cerebral cortex after one, three and five years, as compared with those who had lower maximum oxygen uptake. But we didn't find any effect from increasing fitness during the study," says Håberg.

The cerebral cortex is the outermost layer of the brain and is important for several important brain functions, such as attention, ability to make choices, working memory, abstract thinking and memory. This part of the brain becomes thinner with age, and thinning of the cerebral cortex in different areas is linked to different types of dementia, such as Alzheimer's disease and frontotemporal dementia.

Fitness more important than type of exercise

All 70- to 77-year-olds in Trondheim were invited to the Generation 100 study in 2012. Those who agreed to participate were randomly assigned to five years of exercise of various kinds. One group would primarily do high intensity intervals, a second group would mainly go for walks or do other exercise with moderate intensity, and the last group would try to follow the activity recommendations of the health authorities to be physically active for at least 150 minutes each week.

The first two groups were followed up most closely by the researchers, and were offered two organized training sessions each week. The NTNU researchers looked beyond the connection between fitness and brain health and also investigated whether the type of training follow-up that participants received made a difference.

"Our results show that organized training follow-up may have given older men, but not older women, better cognitive function and lowered the probability of mild cognitive impairments. But all in all, it seems that the most important thing is that you actually train in a way that increases your fitness, regardless of whether you get organized help to be physically active or not," says Zotcheva.

Less brain atrophy than expected

"In the groups that received follow-up with high-intensity training and training with moderate intensity, respectively, we found somewhat greater loss of brain volume in deep areas of the brain than among those who trained themselves. But we have to emphasize that everyone in the Generation 100 study—regardless of the form of exercise they did—had less brain loss than expected for people in their 70s. The group that trained on their own without organized follow-up had the least shrinkage in the hippocampus and thalamus," Håberg says.

The training follow-up in Generation 100 was not decisive for the participants' ability to solve cognitive tasks.

"The groups that were able to attend organized training didn't perform any better than the group that trained on their own on various tasks, such as remembering where an object is located, memorizing words, processing information quickly or planning," says Håberg.

Maintained good cognitive function

"It's still worth noting that the 70- to 77-year-old participants on average had the same cognitive abilities after five years as at start-up, and that during the study period they even improved on some of the tests. The results show that being in good shape like the Generation 100 participants were, is important for maintaining good brain function," Håberg says.

The training effect thus seems to be greatest for people who enter retirement age in good shape, and exercise that improves fitness can provide further benefits. So how should the elderly train to get in better shape?

"Several paths can lead to that goal, and the most important factor is to find an activity you enjoy and can continue with over time. In order to maintain or increase your fitness, you should in any case exercise regularly in a way that gets you out of breath and sweaty," says Zotcheva.

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More information: Ekaterina Zotcheva et al, Effects of 5 Years Aerobic Exercise on Cognition in Older Adults: The Generation 100 Study: A Randomized Controlled Trial, Sports Medicine (2021). DOI: 10.1007/s40279-021-01608-5

Daniel R. Sokołowski et al, 5 Years of Exercise Intervention Did Not Benefit Cognition Compared to the Physical Activity Guidelines in Older Adults, but Higher Cardiorespiratory Fitness Did. A Generation 100 Substudy, Frontiers in Aging Neuroscience (2021). DOI: 10.3389/fnagi.2021.742587

Jasmine Pani et al, Effect of 5 Years of Exercise Intervention at Different Intensities on Brain Structure in Older Adults from the General Population: A Generation 100 Substudy, Clinical Interventions in Aging (2021). DOI: 10.2147/CIA.S318679

Provided by Norwegian University of Science and Technology